The role played by viruses in the production of human and animal disease was readily recognized in the past due to their ability to cause cell and tissue destruction with concomitant physiologic and cytologic changes. This cytolytic effect plays a prominent role in the pathogenesis of many viral diseases. It has been shown, however, that viruses may alter cells in ways other than those leading to cell death, adding a new dimension to the studies of viral pathogenesis. In view of this, a study of non-cytolytic virus infections, particularly virus induced malignant transformation, is underway to develop an integrated program which investigates the results of virus infection and transformation on non-differentiated and differentiated tissues, primarily the salivary glands. These tissues are particularly important in the ecology of the oropharynx since a relationship is known to exist between the functional status of the gland and the environment of the oral cavity. Not only can the obvious relationships, such as the ability of the gland cells to serve as a substrate for virus replication, be examined but other factors as well. Since the salivary glands are tissues made of many cell types, the results of infection may be examined in these different cells from various points of view. The cell metabolism will be studied and related to gland functions such as uptake of metabolites, production of salivary enzymes, characteristics of the enzymes and their release, response to stimuli, lipid metabolism, and the effects of virus infection on these processes. The use of non- cytolytic viruses such as polyoma virus is well suited to this since the infected cells may retain normal type functions as well as acquiring new or altered properties. The problem is to elucidate the changes that occur in salivary glands and mechanisms by which they are brought about. The role of virus induced changes in diseases of the salivary glands offers an attractive area for immediate and future study.